The objective of the proposed program is to gain an understanding of the molecular basis of tissue specific intercellular adhesion. Attention is focused on the adhesive properties of embryonic, adult, and neoplastic liver cells from chick, rat and mouse. The adhesive specificity of these cells is being studied using specific cell adhesion assays. The properties and specificity of these assay procedures are being studied in detail. Refinement of existing assay procedures may lead to methods for studying the more subtle cell type interactions underlying histogenic organization. Other studies are directed at the identification, isolation and characterization of the tissue specific cell ligands responsible for adhesive specificity. Species and organ specific antisera have been prepared which block tissue specific intercellular adhesion. The antisera are being used to identify the adhesion ligands of embryonic liver cells. Purification comparative characterization, and quantitation of the liver specific adhesion ligands responsible for organ specific cell:cell adhesion is the ultimate goal. Hybridomas producing monoclonal antisera directed against the "differentiation antigens" of embryonic liver will be prepared. Among these cell surface antigens are the adhesion ligands. Control of the transmembrane proteins of the cell surface by cytoskeletal elements is also being investigated. The regulation of intercellular adhesion during development and neoplastic alterations is being studied. The possibility that hepatoma cells escape "social" restrictions (regulation of division, movement, differentiation, and adhesion properties) will be examined. The study of tissue specific adhesive behavior of cells represents an approach to an analysis of the complex problem of tissue homeostasis. The "asocial" behavior of neoplastic cells is a fundamental property but probably represents secondary alterations of the primary events of oncogenesis. Nevertheless, an analysis of intercellular adhesion may yield an understanding of many important phenomena, such as the underlying basis for loss of growth control and/or metastases.